Triethylamine → (R*)-3-[1-((R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl)piperidin-3-yl]benzoic acid methyl ester

HRID 2407248Notes

Reaction equation

HRID 2407248 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[C:11](Cl)=[O:12].[CH3:14][O:15][C:16](=[O:29])[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]2)[CH:18]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:14][O:15][C:16](=[O:29])[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:11]([C@@H:2]3[O:1][C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=4[O:4][CH2:3]3)=[O:12])[CH2:24]2)[CH:18]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7022160(R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl chlorideHCID 12937924Methyl 3-(piperidin-3-yl)benzoate

Product 1

HCID 68489387(R*)-3-[1-((R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl)piperidin-3-yl]benzoic acid methyl esterYield 21.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl chloride (240 mg, 1.21 mmol) in DCM (5 ml) was added to an ice-cold mixture of 3-(piperidin-3-yl)benzoic acid methyl ester (267 mg, 1.21 mmol), triethylamine (59 mg, 0.58 mmol) and DCM (10 ml). After stirring for 2 h at RT, the mixture was washed with 1 M HCl (10 ml) and 1 M Na2CO3. The organic phase was dried over Na2SO4 and evaporated to dryness and the residue was purified by flash chromatography using heptane/EtOAc as eluent. The first eluting diastereomer was collected to afford 98 mg of the title compound.

Workup

  1. washthe mixture was washed with 1 M HCl (10 ml) and 1 M Na2CO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated to dryness
  4. customthe residue was purified by flash chromatography
  5. customThe first eluting diastereomer was collected

Sources & evidence

ORD record
ord-5fa2c526107b4b0c8fdf6d869898b68a
Source dataset
uspto-grants-2014_08
Patent number
US08809536B2

Reaction notes

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